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Major role of dihydropyridine-sensitive Ca2+ channels in Ca(2+)-induced calcitonin secretion
H Scherübl1, T Kleppisch, A Zink
1Pharmakologisches Institut, Freie Universität Berlin, Germany.
Abstract:
Endocrine cells are known to possess multiple types of Ca2+ channels. In neurons, omega-conotoxin-sensitive N-type Ca2+ channels have been shown to play a dominant role in neurotransmitter release, but uncertainty remains about the types of Ca2+ channels involved in stimulus-secretion coupling in endocrine cells. We investigated the relative contribution of 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channels to Ca(2+)-induced calcitonin release in parafollicular cells of the thyroid (C cells). In whole cell voltage-clamp experiments, both 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channel currents were identified. The dihydropyridine isradipine (1 microM) but not omega-conotoxin (1 microM) inhibited the steady-state Ca2+ influx at physiological membrane potentials, the spontaneous electrical activity, and calcitonin secretion (at 2-h incubations). Moreover, suppression of the spontaneous electrical activity by the Na+ channel blocker tetrodotoxin did not affect calcitonin release. We conclude that 1,4-dihydropyridine-sensitive Ca2+ channels play a major role in Ca(2+)-dependent calcitonin release and that calcitonin secretion due to Ca2+ influx proceeds even in the absence of action potentials.
Insights
1,4-dihydropyridine-sensitive calcium channels are key for calcitonin release from thyroid C cells. This calcium influx drives secretion, independent of neuronal action potentials.
Area of Science:
- Endocrinology
- Cell Physiology
- Neurobiology
Background:
- Endocrine cells utilize various calcium (Ca2+) channels for secretion.
- N-type Ca2+ channels are crucial for neurotransmitter release in neurons, but their role in endocrine secretion is less understood.
Purpose of the Study:
- To determine the specific roles of 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channels in Ca2+-induced calcitonin release from thyroid C cells.
Main Methods:
- Whole-cell voltage-clamp electrophysiology to identify Ca2+ channel currents.
- Application of isradipine (a 1,4-dihydropyridine) and omega-conotoxin.
- Measurement of Ca2+ influx and calcitonin secretion.
- Use of tetrodotoxin to block Na+ channels.
Main Results:
- Both 1,4-dihydropyridine-sensitive and omega-conotoxin-sensitive Ca2+ channel currents were detected in C cells.
- Isradipine significantly inhibited steady-state Ca2+ influx, spontaneous electrical activity, and calcitonin secretion.
- Omega-conotoxin did not inhibit these processes.
- Tetrodotoxin-induced suppression of electrical activity did not affect calcitonin release.
Conclusions:
- 1,4-dihydropyridine-sensitive Ca2+ channels are the primary mediators of Ca2+-dependent calcitonin release.
- Calcitonin secretion can occur via Ca2+ influx independently of action potentials in C cells.